Biomedical subjects

R A Kandel

Publications and source records attributed to R A Kandel.

At least 37 records · Page 2Linked to original sources

PubMed1998

MR imaging of symptomatic osteochondromas with pathological correlation.

OBJECTIVE: To demonstrate the value of MR imaging in the diagnosis and differentiation of the various symptomatic complications of osteochondromas, providing pathological correlation with emphasis on the usefulness of MR imaging as a single imaging modality in these patients. DESIGN: We retrospectively reviewed all MR examinations of clinically symptomatic osteochondromas (30 patients) performed at our institution between March 1990 and October 1997. PATIENTS: Thirty patients had clinically symptomatic osteochondromas during the study period. Twenty patients were male and 10 were female. There were five cases of multiple osteochondromatosis. Pathological correlation was available in 24 patients. RESULTS AND CONCLUSION: Symptomatic complications included fracture (7%), osseous deformity limiting range of motion (23%), vascular injury (7%), neurological compromise (10%), bursa formation (27%) and malignant transformation (27%). MR imaging was able to diagnose or suggest the etiology for the clinical symptomatology in all cases, demonstrating that it is an ideal imaging modality in the diagnostic evaluation of symptomatic complications of osteochondromas and often avoids the need for further imaging.

Adolescent↗

PubMed1998

Rhabdomyosarcoma with rhabdoid-like features.

We describe an unusual case of a rhabdomyosarcoma (RMS) in that it had rhabdoid-like cells histologically and occurred in a female who had undergone bone marrow transplantation for chronic myelogenous leukemia. The tumor was composed of loosely cohesive cells with abundant eosinophilic cytoplasm and exhibited PAS-negative paranuclear inclusions. The tumor cells had positive vimentin, muscle-specific actin, sarcomeric actin and desmin immunoreactivity. Ultrastructurally, the tumor cells contained aggregates of thin and thick filaments. In situ hybridization did not detect human papillomavirus or cytomegalovirus DNA, or EBV DNA or RNA. The tumor fulfilled the current criteria for a diagnosis of RMS; however, it could not be further classified. The tumor appears to have a good prognosis as there has been no evidence of recurrence five years after resection. As this is the first case report, to our knowledge, of this type of tumor following bone marrow transplant, the significance of this association is not yet clear.

Abdominal Neoplasms↗

PubMed1997

The impact of residual disease on local recurrence in patients treated by initial unplanned resection for soft tissue sarcoma of the extremity.

BACKGROUND AND OBJECTIVES: "Unplanned excision" in soft tissue sarcoma (STS) is defined as the gross removal of tumor without preoperative staging or consideration of the need for removal of normal tissue around the tumor. This study evaluated whether unplanned excision in patients with extremity STS would have an impact on local relapse (LR), even if reexcision of the tumor bed was undertaken. METHOD: Two hundred thirty-nine (239) patients with primary, extremity STS treated with limb salvage surgery were included in this study. Of the 239, 78% were treated with surgery and irradiation. Forty-seven tumors were low-grade and 192 high grade. Mean tumor diameter was 7.5 cm. Twenty had local recurrences and 64 relapsed systemically. RESULTS: Only margin and prior surgery were significant in univariate analysis (P < 0.05, log-rank test). The Cox multivariate analysis revealed that both margin of resection (P < 0.001) and the status of the local tumor site (P < 0.05) at definitive surgery were significant predictors of local relapse. CONCLUSIONS: These results suggest that the presence of microscopic disease in the reexcised specimen following unplanned resection is a risk factor for local disease recurrence.

Adolescent↗

PubMed1997

Chondroblastoma with multiple distant soft tissue metastases.

A case of metachronous distant soft tissue metastases from a primary rib chondroblastoma, occurring in a 60-year-old man 17 years following resection of the initial lesion, is described. Metastatic chondroblastomas are very rare and almost always involve the lungs. Discussed herein are the clinical, radiologic, and pathologic findings of this unusual case with comparison of our findings to other reports of metastasizing chondroblastomas.

Bone Neoplasms↗

PubMed1997

In vitro formation of mineralized cartilagenous tissue by articular chondrocytes.

Study of the deep articular cartilage and adjacent calcified cartilage has been limited by the lack of an in vitro culture system which mimics this region of the cartilage. In this paper we describe a method to generate mineralized cartilagenous tissue in culture using chondrocytes obtained from the deep zone of bovine articular cartilage. The cells were plated on Millipore CMR filters. The chondrocytes in culture accumulated extracellular matrix and formed cartilagenous tissue which calcified when beta-glycerophosphate was added to the culture medium. The cartilagenous tissue generated in vitro contains both type II and type X collagens, large sulfated proteoglycans, and alkaline phosphatase activity. Ultrastructurally, matrix vesicles were seen in the extracellular matrix. Selected area electron diffraction confirmed that the calcification was composed of hydroxyapatite crystals. The chondrocytes, as characterized thus far, appear to maintain their phenotype under these culture conditions which suggests that these cultures could be used as a model to examine the metabolism of cells from the deep zone of cartilage and mineralization of cartilagenous tissue in culture.

Alkaline Phosphatase↗

PubMed1997

Composition of cartilagenous tissue with mineralized and non-mineralized zones formed in vitro.

We have previously shown that cartilagenous tissue with both non-mineralized and mineralized zones can be formed by chondrocytes which have been selectively isolated from the deep zone of bovine articular cartilage. In this study, we quantitate proteoglycan and collagen content, calcification, tissue thickness and cellularity over a 10 week culture period in order to study matrix accumulation and tissue formation. The cartilagenous tissue cellularity and proteoglycan and collagen accumulation continued up to 8 weeks and this was paralleled by an increase in tissue thickness. The amount of mineral in the tissue as well as the amount of collagen, in contrast to proteoglycan, was still increasing at 10 weeks. At the end of week 10, the amount of glycosaminoglycan and collagen as a percentage of dry weight of the tissue were 11.0 +/- 0.6% and 14.8 +/- 0.1%, respectively, compared with 10.5 +/- 1.2% and 35.1 +/- 5.8% for the in vitro deep articular cartilage. The amount of calcium as a percentage of dry weight of the cartilagenous tissue was 8.1 +/- 0.7% which was similar to the in vivo cartilage (9.1 +/- 1.6%). This data suggests that 8 weeks of culture may be necessary before the cartilagenous tissue is suitable for use as a transplant.

Animals↗

PubMed1996

SAS is amplified predominantly in surface osteosarcoma.

The development of several types of human tumors is related to amplification of genes that are involved in cell growth. The protein products of these genes give the cells a selective growth advantage. The q13-15 region of chromosome 12 is frequently altered in human sarcomas, and the SAS gene has been identified in an amplification unit mapping to this region. Gene amplification of SAS was analyzed to determine the frequency of genetic alteration of this gene in osteosarcoma. Using Southern blot analysis as well as quantitative polymerase chain reaction, SAS was found to be amplified in 10 (36%) of 28 osteosarcomas. Gene amplification was evaluated in subtypes of osteosarcoma. All seven surface osteosarcomas displayed amplified SAS. In contrast, SAS was amplified in only two (13%) of 15 intramedullary osteosarcomas. The finding that all surface osteosarcomas demonstrated SAS gene amplification suggests that this gene may play a role in the pathogenesis of osteosarcoma subtypes and that surface osteosarcoma may be genetically different from high-grade intramedullary osteosarcoma.

Blotting, Southern↗

PubMed1996

Titanemia from total knee arthroplasty. A case resulting from a failed patellar component.

The subject of this case report is a patient with elevated serum levels of titanium (77 parts/billion [ppb]; normal, 3.3 ppb) and vanadium (0.38 ppb; normal, 0.17 ppb) resulting from excessive wear of a metal-backed patellar component in a total knee arthroplasty. The patellar component was worn through both its polyethylene and metal backing as a result of abnormal contact between the patellar and femoral components. Scanning electron microscopic examination of the ingrowth surface of the patellar component indicated that particle debonding occurred as a result of overloading of the sintered neck regions at the particle-substrate interface, suggesting a possible damage during initial insertion of the device, which may have predisposed it to loosening and abnormal contact with the femoral component. Wear particles resulted in staining of the tissues within the knee and an inflammatory and immune response in the synovium consisting of giant cells and T lymphocytes. The serum metal levels were reduced 22 weeks after replacing the patellar component; however, the titanium level was still slightly elevated (8 ppb).

Aged↗

PubMed1996

Primary leiomyosarcoma of bone: report of seven cases and review of the literature.

OBJECTIVE: To report seven cases of intraosseous leiomyosarcoma and compare them with the cases in the literature. DESIGN: Retrospective review of histologic, immunohistochemical, and ultrastructural features. Tumors were examined immunohistochemically for proliferative activity and p53 protein accumulation. SETTING: Mount Sinai Hospital, University of Toronto, Ontario, Canada. RESULTS: The histologic grade of the tumors ranged from I to III. All tumors showed vimentin and muscle-specific actin immunoreactivity and smooth muscle differentiation ultrastructurally. Proliferative activity was demonstrated immunohistochemically in five of the seven cases. Only one tumor showed p53 protein accumulation. CONCLUSION: Primary leiomyosarcoma of bone is an aggressive tumor with light microscopic, ultrastructural, and immunohistochemical features similar to leiomyosarcoma of soft tissue. The proliferative activity of these tumors does not appear to correlate with the histologic grade. p53 protein accumulation as detected by immunostaining is not common in these tumors.

Actins↗

PubMed1995

Characterization of proteoglycan accumulation during formation of cartilagenous tissue in vitro.

In order to study proteoglycan retention and accumulation, we optimized a chondrocyte cell culture system in which isolated bovine articular chondrocytes accumulate extracellular matrix to form a continuous layer of cartilagenous tissue. The tissue can attain a thickness of up to 110 microns by 35 days. The cells synthesize large keratan sulfate containing proteoglycans and type II collagen indicating that the chondrocytes maintain their phenotype in these culture conditions. Matrix accumulation is enhanced by increased cell density and the presence of serum and ascorbic acid. The amount of proteoglycans synthesized by the chondrocytes increases up to day 21 and then decreases to the same levels as are synthesized during the first week of culture. The percentage of newly synthesized proteoglycans retained in the matrix increases from 20% on day 6 to a maximum of 85% by day 35. The proteoglycan and collagen content in the tissue increases with time in culture. The changes in the percentage of proteoglycans retained parallels the increase in proteoglycan content. After day 35, there is no further increase in the amount of proteoglycans and collagen nor in the percentage of newly synthesized proteoglycans retained in the extracellular matrix. These studies demonstrate that the cultures are going through two phases: one of matrix accumulation and then one of maintaining the existing matrix. The period of matrix accumulation occurs between days 10-21 whereas matrix maintenance is observed after day 35. Using this culture system to study proteoglycan accumulation and maintenance during these culture periods may prove useful in identifying the mechanisms regulating these processes.

Animals↗

PubMed1995

Correlation of p-glycoprotein detection by immunohistochemistry with mdr-1 mRNA levels in osteosarcomas. Pilot study.

All the factors that influence prognosis in patients with osteosarcomas have not been fully determined. One reported predictor of poor outcome is increased multi-drug resistant gene (mdr-1) expression, as measured by reverse transcription and polymerase chain reaction (RT-PCR). We examined whether immunostaining for p-glycoprotein, the protein product of mdr-1, could be used instead of RT-PCR to indicate the presence of the multidrug-resistant phenotype. The sensitivity of the immunostaining was determined using KB cell sublines. For 13 cases of osteosarcoma, samples were immunostained for p-glycoprotein and the levels of mdr-1 expression quantitated with use of RT-PCR. Three osteosarcomas with undetectable levels of mdr-1 expression by RT-PCR were negative immunohistochemically. Ten cases showed mdr-1 expression ranging from approximately 1 to 32 copies of mdr-1 mRNA/cell. Of these cases, five cases contained occasional tumour cells with positive immunostaining. There was no correlation between levels of expression and the presence or number of immunoreactive cells. These results indicate that the presence of p-glycoprotein immunostaining does not reliably correlate with the level of mdr-1 expression. However it may be useful in conjunction with RT-PCR to further define different subgroups of osteosarcomas that may have different prognoses, and this is currently under investigation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Effect of Mycoplasma arthritidis superantigen on enzymatically induced arthritis in mice.

The objective of this study was to examine the effect of the stimulation of the immune system with Mycoplasma arthritidis superantigen (MAS) on joint inflammation and cartilage destruction. MAS was administered either alone or combined with a model of degenerative arthritis induced by intraarticular injection of collagenase enzyme. Intraperitoneal injection of MAS resulted in activation of peripheral lymphocytes in BALB/c mice, as shown by a proliferative response of splenocytes isolated from MAS-treated animals to IL-2-containing supernatant. Intraperitoneal or intra-articular administration of MAS alone at concentrations maximally activating lymphocytes had no detectable effect on joints. Intra-articular injection of collagenase resulted in some infiltration of inflammatory cells into the joints, hyperplasia and hypertrophy of synovial lining, pannus formation and surface loss of proteoglycans 7 days following the injection. At 21 days, the animals showed almost total loss of cartilage and minimal or no inflammation. Animals receiving MAS in addition to collagenase treatment showed similar changes in the joints. These data have demonstrated that activation of the immune system with MAS in vivo does not increase joint inflammation or cartilage degradation in enzymatically induced arthritis.

Animals↗

PubMed1995

Transplantation of cartilagenous tissue generated in vitro into articular joint defects.

The purpose of this pilot study was to determine whether isolated rabbit chondrocytes will form cartilagenous tissue in culture and whether this tissue can be used as a cartilage transplant in order to resurface damaged joints. Chondrocytes were isolated from rabbit articular cartilage, plated as a monolayer on Millicell-CMR filters and maintained in cell culture. The cells formed cartilagenous tissue that could be removed from the filter support by two weeks in culture. The chondrocytes synthesize type II collagen indicating that they maintained their phenotype under these conditions. For the transplant studies, two types of articular surface defects, either full thickness into subchondral bone or intra-chondral, were created in rabbits. The cartilagenous tissue was placed in the defect either without fixation or with the topical application of an adhesive agent (Cell-Tak or Nexaband Avian). The joints were examined within two weeks following the surgery. No transplants remained in the defects in those animals in which tissue fixation had been attempted with Cell-Tak. Those grafts fixed into the cartilage defect with Nexaband Avian remained in place but consisted of a condensed layer of acellular tissue. However, cartilagenous tissue was present and intact in five of the six animals in which the transplant had been placed, in the absence of adhesive, into a full thickness defect. In conclusion, cartilagenous tissue generated in vitro can survive transplantation but an appropriate method to fix grafts into intra-chondral defects is required.

Animals↗

PubMed1994

Lipocortin 2 (annexin 2) is a major substrate for constitutive tyrosine kinase activity in chondrocytes.

Treatment of cultured bovine articular chondrocytes with 100 microM orthovanadate, in the absence of serum, results in the production of a single major tyrosine phosphorylated protein with an apparent molecular mass of 36 kDa (p36). Chondrocytes were found to contain proteins reactive with anti-lipocortin 1, 2, and 5 antibodies. p36 comigrated on SDS-polyacrylamide gels with lipocortin 2, but not with other members of the lipocortin family. The distribution of p36 between the particulate and soluble cell fractions was also similar to that of lipocortin 2. p36 that was purified on an anti-phosphotyrosine immunoaffinity column cross-reacted with anti-lipocortin 2 antibodies. Similarly, lipocortin 2 purified on an anti-lipocortin 2 immunoaffinity column reacted with anti-phosphotyrosine antibodies. Furthermore, cyanogen bromide cleavage fragments of purified lipocortin 2 and p36 were similar. These data demonstrate that the major constitutively tyrosine phosphorylated protein, in chondrocytes, is lipocortin 2. Tyrosine phosphorylated p36 required SDS buffers for extraction due to a loss of the tyrosine phosphate group under other solubilization conditions using Triton X-100 or sodium cholate. This study provides a system for the study of the effects of tyrosine phosphorylation on lipocortin 2 function. What role lipocortin 2 plays in chondrocyte biology remains to be determined.

Animals↗

PubMed1993

Effect of phorbol ester on the inhibition of proteoglycan synthesis induced by interleukin 1 and antiinflammatory drugs.

Low (2 ng/ml) and high (40 ng/ml) concentrations of the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA) were tested for their effect on cultured bovine articular chondrocyte proteoglycan synthesis. In addition, we examined whether PMA could reverse interleukin 1 (IL-1) and nonsteroidal antiinflammatory drug (NSAID) induced inhibition of proteoglycan synthesis. Low concentrations of PMA stimulated proteoglycan synthesis by chondrocytes. High concentrations of PMA had no significant effect. IL-1 and high concentrations of NSAID inhibited proteoglycan production by chondrocytes. Low concentrations of PMA completely reversed IL-1 induced inhibition but did not significantly alter proteoglycan synthesis in the presence of antiinflammatory drugs. On the other hand, high concentrations of PMA had little effect on IL-1 induced inhibition but significantly potentiated the suppression of proteoglycan synthesis induced by 2 of the NSAID tested, indomethacin and flurbiprofen. Assay of PKC activity indicated that PKC levels were down-regulated by high but not by low concentrations of PMA. This suggests that different mechanisms were regulating the effects of low and high concentrations of PMA on proteoglycan synthesis. Although IL-1 and high concentrations of NSAID both suppress proteoglycan synthesis by chondrocytes, their different responses when coincubated with PMA suggest that they act through different pathways.

Animals↗

PubMed1993

Calcium ionophore A23187 stimulates production of a 144 kDa gelatinase.

To determine whether intracellular calcium could be involved in regulating gelatinase production, bovine synovial fibroblasts were incubated with the calcium ionophores A23187 or ionomycin. Addition of calcium ionophore stimulated production of a gelatinase with an apparent molecular weight of 144 kDa. To ensure that the calcium ionophore was elevating cytosolic free calcium levels, calcium levels were determined using Indo-1. Addition of 0.1 microM ionomycin raised [Ca2+]i up to 1053 +/- 163 nM (mean +/- SD). Our data shows that calcium ionophore A23187 stimulates production of a high molecular weight gelatinase. The appearance of p144 gelatinase correlates with an increase in intracellular calcium.

Animals↗

PubMed1992

Interleukin 1 and phorbol 12-myristate 13-acetate induce collagenase and PGE2 production through a PKC-independent mechanism in chondrocytes.

In the present study we demonstrate that interleukin 1 (IL 1) and phorbol 12-myristate 13-acetate (PMA) stimulate collagenase production by bovine chondrocytes in monolayer culture. Since it has been well established that PMA stimulates protein kinase C (PKC), we examined whether IL 1 and PMA also stimulate PKC in chondrocytes. In agreement with other studies, PMA induced the translocation of PKC, reflecting PKC activation by PMA. In contrast, IL 1 did not induce the translocation of PKC. Both IL 1 and PMA stimulated the release of [14C]arachidonic acid from chondrocyte phospholipids, suggesting that both agents stimulate phospholipase A2 (PLA2). Concomitantly, IL 1 and PMA also induced a pronounced increase in the production of PGE2. Pre-incubation of chondrocytes with staurosporine, a PKC inhibitor, did not affect the stimulation of collagenase production by IL 1 and only minimally that induced by PMA. Similarly, high concentrations of staurosporine did not inhibit prostaglandin E2 (PGE2) production induced by IL 1 or PMA. These data show that IL 1 and PMA stimulate the PLA2 pathway and collagenase production, however, these processes can occur in the absence of PKC activation.

Alkaloids↗

PubMed1992

Prevalence of human papillomavirus in sinonasal papillomas: a study using polymerase chain reaction and in situ hybridization.

Inverted and fungiform papillomas of the sinonasal cavity share a common origin from the Schneiderian membrane, but they differ widely in their rates of recurrence and progression to carcinoma. To determine the role of human papillomavirus in the etiology of these lesions, 15 inverted papillomas, five fungiform papillomas, and two squamous cell carcinomas associated with inverted papilloma were examined for the presence of HPV by in situ hybridization (ISH) and polymerase chain reaction (PCR). ISH was carried out on formalin-fixed, paraffin-embedded material using HPV types 6/11, 16/18, and 31/33/35 DNA probes. Tissue DNA was amplified by PCR with HPV L1 consensus primers, and the product was detected by gel electrophoresis, Southern blotting, and hybridization with type specific probes (HPV types 6/11, 16, 18). Three of 15 inverted papillomas and two of five fungiform papillomas were positive for HPV 6/11 by ISH, whereas PCR detected HPV 6/11 sequences in two of 15 inverted and three of five fungiform papillomas. Biopsies from two patients who had serial resections contained HPV 6/11 in the original lesions and all recurrences. No HPV was detected in the carcinomas by ISH, whereas PCR detected HPV 16 in one carcinoma. These findings confirm the presence of HPV DNA sequences in both inverted and fungiform sinonasal papillomas as well as in an associated squamous carcinoma. This would suggest a role for HPV in the pathogenesis of Schneiderian membrane lesions. Furthermore, our data indicate that ISH and PCR are equally sensitive in detecting HPV in sinonasal papillomas.

Adult↗